ABSTRACT Abstract Background Liposomal formulations of anthracyclines appear to have favorable toxicity profile when compared with conventional anthracyclines in elderly, high risk cardiac patients and patients with prior use of anthracyclines. Randomized controlled trials have evaluated the efficacy and safety profile of liposomal formulations with conventional anthracyclines. Our aim is to evaluate the adverse effects and quantify the relative safety profile of the liposomal and conventional anthracyclines through meta-analysis of the published randomized trials. Methods We conducted a broad search strategy of major electronic databases. We performed a meta- analysis of adverse effects on randomized controlled trials comparing liposomal formulation and conventional anthracyclines on different tumors. The primary outcome was the adverse effects including congestive heart failure (CHF), hematological toxicity, palmar-plantar erythrodysthesias (PPE), alopecia, nausea and vomiting. The odds ratios of the adverse effects were calculated separately and the overall odds ratio of the pooled data was calculated. Results We identified nine randomized controlled trials comparing liposomal formulations and conventional anthracyclines. The study included 2220 patients, of which1112 patients were treated with liposomal formulations and 1108 were treated with conventional anthracyclines. We found that the liposomal formulations have low incidence of CHF(OR 0.34, 95% CI, 0.24–0.47), alopecia (OR 0.0.25, 95% CI, 0.0.10-0.62), neutropenia (OR 0.62, 95% CI, 0.45- 0.85),(OR 0.89, 95% CI, 0.71-1.125), and thrombocytopenia (OR 0.87, 95% CI, 0.61-1.25). The incidence of PPE was similar in both arms (OR 1.08, 95% CI, 0.11- 10.30). Conclusions Liposomal doxorubicin and pegylated liposomal doxorubicin demonstrated favorable toxicity profiles with better cardiac safety and less myelosuppression, alopecia, nausea and vomiting compared with the conventional anthracyclines. The better therapeutic index of liposomal anthracyclines without compromising the efficacy makes it a favorable choice over conventional anthracyclines in elderly patients, patients with risk factors for cardiac disease and patients with prior use of anthracyclines.